Active Site Flexibility

β‐Glucuronidase, GUS, enzymes in the gastrointestinal tract are involved in maintaining mammalian‐microbial symbiosis and can play key roles in drug efficacy and toxicity. Parabacteroides merdae GUS was identified as an abundant mini‐Loop 2, mL2, type GUS enzyme in the Human Microbiome Project gut metagenomic database.

Published in Protein Science, researchers in the Redinbo Group report the crystal structure of P. merdae GUS and highlight the differences between this enzyme and extant structures of gut microbial GUS proteins. They found that P. merdae

GUS exhibits a distinct tetrameric quaternary structure and that the mL2 motif traces a unique path within the active site, which also includes two arginines distinctive to this GUS.

Group members observed two states of the

P. merdae

GUS active site. A loop repositions itself by more than 50 Å to place a functionally‐relevant residue into the enzyme's catalytic site. Finally, they found that P. merdae

GUS is able to bind to homo and heteropolymers of the polysaccharide alginic acid.

Together, these data broaden the understanding of the structural and functional diversity in the GUS family of enzymes present in the human gut microbiome and point to specialization as an important feature of microbial GUS orthologs.